{"paper_id":"cafb44e4-ba64-40a4-bf56-7595a419a790","body_text":"ORIGINAL ARTICLE\nAL-ANBAR MEDICAL JOURNAL\nAnb. Med. J. 20(1): 108–112, 2024\nThe Correlation of Restless Leg Syndrome with Endometriosis: A Cross-Sectional\nStudy\nMufeed Akram Taha\n∗\nDepartment of Medicine/Neurology, College of Medicine, University of Kirkuk, Kirkuk, Iraq.\n(Received : 5 March 2024; Accepted : 6 May 2024; First published online: 30 May 2024)\nABSTRACT\nBackground:\nRestless leg syndrome (RLS) is a common neurological disorder, but its correlation\nwith endometriosis remains unclear.\nObjectives:\nTo evaluate the correlation of RLS with endometriosis.\nMaterials and methods:\nA cross-sectional study included 155 patients who were diagnosed with\nRLS at the Neurology Department, Azadi Teaching Hospital, Kirkuk, Iraq. The study started on\n1\nst\nJune 2020 and ended on 1\nst\nMarch 2023. RLS was diagnosed using the criteria established\nby the International Restless Leg Syndrome Study Group (IRLSSG). The researchers questioned\nthe patients about their history of endometriosis. Then categorized into two groups. The first\ngroup consisted of 72 cases with surgically confirmed endometriosis, whose severity was determined\nby the Gynecologists following the guidelines of the revised American Society of Reproductive\nMedicine (rASRM). The remaining 83 cases formed a group comprising individuals with RLS\nwithout endometriosis. We collected data from each participant about their age, marital status,\nsmoking habit, and body mass index (BMI).\nResults:\nOne hundered fifty five patients with a mean age of 29.19\n±\n6.12 years were diagnosed\nwith RLS. There was a statistically significant difference (P-value = 0.029) between the RLS and\nthe age of the patients with endometriosis compared to those without endometriosis. However,\nthere were no significant statistical differences (P-value\n>\n0.05) in marital status, smoking habits,\nor BMI between the two groups. In terms of RLS severity ratings, patients with endometriosis\ntended to have more severe rating scales compared to those without this condition. Additionally,\na Pearson’s correlation test showed a strong positive correlation, between IRLSSG and rASRAM\nscores (P-value = 0.0001, r = 0.7).\nConclusion:\nRLS was strongly and positively correlated with endometriosis. However, the exact\ncause and nature of this correlation remained obscure.\nKeywords:\nRestless leg syndrome; Endometriosis; Correlation\nDOI:\n10.33091/amj.2024.147487.1618\n©\n2024, Al-Anbar Medical Journal\nINTRODUCTION\nR\nestless legs syndrome (RLS) is a disorder, often\noverlooked, characterized by painful sensations\nprimarily in the legs during rest and relieved by\nmovement [\n1\n]. RLS can significantly impact one’s\nquality of life by causing pain and disrupting sleep, with a\nprevalence of 5-15% [\n2\n]. The condition tends to be more\ncommon among adults with a female predominance and is\n∗\nCorresponding author: E-mail:\nmufeedakram@uokirkuk.edu.iq\nThis is an open-access article under the CC BY 4.0 license\ndivided into two types: primary RLS (also called idiopathic\nRLS) and secondary RLS which is linked to several factors\nsuch as pregnancy, iron deficiency anemia, and chronic renal\nor neurological disease. Both types had the same symptoms\nand diagnostic criteria [\n3\n]. In addition, endometriosis can af-\nfect the nerves by causing pressure effects that lead to pain\nsensations, and therefore, the overlap of symptoms can make\nthe diagnosis difficult [\n4\n].\nEndometriosis, a chronic progressive disease with a preva-\nlence of 10%, commonly affects women of reproductive age\nand regresses with menopause, manifesting through a variety\nof recurrent symptoms like chronic pelvic pain, painful men-\nstruation, subfertility, and pain during intercourse or defeca-\n108\nhttp://doi.org/10.33091/amj.2024.147487.1618\n\nRestless Leg Syndrome and Endometriosis Anb. Med. J. 20(1), 2024\ntion [5]. Endometriosis commonly affects the ovaries [6], and\napproximately one out of every nine women receives a diagno-\nsis at delivery, with the highest occurrence occurring between\nages 25 and 35 year [7].\nThere have been several studies that have explored the as-\nsociation between RLS and various health issues such as hy-\npothyroidism, multiple sclerosis, diabetes mellitus, and poly-\ncystic ovarian syndrome [8–11]. However, only two stud-\nies have investigated the association between RLS and en-\ndometriosis. The first study by Tempest et al. [12] dis-\ntributed a questionnaire to premenopausal women, collecting\ndata on RLS and endomteriosis associated symptoms. The\nstudy did not provide a specific prevalence rate of RLS in\nwomen with endometriosis but mentioned that there was a\nsignificantly higher prevalence of symptoms of RLS in cases\nwith endometriosis compared to those without endometerio-\nsis. The second investigation was by Sumbodo et al. [13] who\ndid not specifically mention the association of RLS with en-\ndometriosis and focused primarily on the relationship between\nsleep disturbances and endometriosis. Therefore, the objec-\ntive of this study was to address this gap by determining the\ncorrelation of RLS in non-pregnant women with endometrio-\nsis.\nMA TERIALS AND METHODS\nAfter collecting informed consent from all patients, a cross-\nsectional study was conducted in the Neurological Depart-\nment at Azadi Teaching Hospital, Kirkuk, Iraq. The study\ncovered the period between 1 st June 2020 and 1 st March\n2023. The current study enrolled 155 consecutive patients\nwith newly diagnosed RLS according to the four-point diag-\nnostic criteria of IRLSSG which include the following: ”Desire\nto move the extremities, usually associated with discomfort\nor disagreeable sensations in the extremities, motor restless-\nness, symptoms worse at rest with at least temporary relief\nby activity, and symptoms worse later in the day or at night”.\nThe Clinical Research Ethics Committee at the College of\nMedicine, University of Kirkuk approved the study with de-\ncision no. 32 on 10.04.2023. The severity of RLS was rated\nusing the IRLSSG rating scale: “(None: 0), (Mild: 1 to 10),\n(Moderate: 11 to 20), (Severe: 21 to 30), and (Very severe:\n31 to 40) points” [14].\nAll cases were asked for a history of endometriosis, 72 of\nthose surgically confirmed had endometriosis and their sever-\nity was labelled by the Gynecologists according to the revised\nAmerican Society of Reproductive Medicine (rASRM) score\n[15], which was classified as (1-5 minimal), (6-15 mild), (16-40\nmoderate) and (> 40 severe endometriosis), while the remain-\ning 83 patients didn’t have endometriosis, who were excluded\nfrom the study after being referred to Gynecologists who ruled\nout the diagnosis of endometriosis based on clinical features\nand in some cases by laparoscopy.\nThe inclusion criteria were women aged 18 to 42 years with\nor without endometriosis who accepted participation in the\nstudy. The exclusion criteria were women with a history of\nspecific chronic diseases, including anaemia, vitamin D defi-\nciency, parkinsonism, hereditary and/or diabetic neuropathy,\nspinocerebellar ataxia, thyroid disorders, hypertension, hy-\nperlipidemia, heart disease, stroke, renal disease, osteoarthri-\ntis, fibromyalgia, rheumatoid arthritis, varicose veins, dia-\nbetes mellitus, and chronic drug users such as hormonal ther-\napy, antidepressants, and antipsychotics, because they could\ncause RLS and affect the results of the study. Besides, pa-\ntients who declined to participate were also excluded from\nthe present study. Data from each patient were registered\nregarding the age, marital state, smoking, and body mass\nindex (BMI) [calculated by the following equation: weight\n(kg)/height (m 2)] [16]. Statistical analysis was done using\nIBM SPSS (Statistical Package for the Social Sciences) ver-\nsion 26. The continuous data were presented as mean value ±\nstandard deviation (SD), and the categorical variables were\nsummarized as numbers (n) and percentages (%). Compar-\nisons between groups were made using Pearson’s Chi-squared\ntest for categorical variables. The Pearson correlation coeffi-\ncient was used to assess the correlation between IRLSSG and\nrASRM. A P-value of < 0.05 was considered a statistically\nsignificant difference.\nRESUL TS\nThe study population characteristics based on RLS status\nwith and without endometriosis are outlined in Table 1. Of\nthe 155 newly diagnosed cases of RLS with a mean age of\n29.19 ± 6.12 years (ranging from 18 to 42 years), 72 patients\nhad RLS along with endometriosis, while 83 patients had RLS\nwithout endometriosis. A significant statistical difference in\nthe age distribution (P-value = 0.029) was observed, with the\nmajority of cases (43.1%) falling within the age range of 25-\n30 years in the group with RLS and endometriosis. However,\nwe found no significant statistical difference between the two\ngroups concerning marital status, smoking habits, and BMI,\nwith P-values of 0.72, 0.35, and 0.35, respectively.\nBy using IRLSSG score scales to assess cases of RLS in both\ngroups, a significant difference (P-value = 0.001) was identi-\nfied, as 44.4% of patients who had endometriosis reported a\nsevere score of RLS, while 31.9% reported very severe symp-\ntoms; this is significantly higher than the corresponding fig-\nures for those without endometriosis (13.3%), as shown in\nTable .\nThe use of the rASRM score to evaluate the severity of\nendometriosis in individuals with RLS revealed that 25%,\n29.17%, 30.56%, and 15.28% had minimal, mild, moderate,\nand severe scores, respectively, as shown in Figure 1.\nThe Pearson correlation coefficient test between the IRLSS\nrating scales of RLS and the severity of endometriosis\n(rASRM) indicated a positive correlation, between them (P-\nvalue = 0.0001, r = 0.7), as indicated in Table and Figure\n2.\nDISCUSSION\nRLS is a common neurological condition that affects ap-\nproximately 5 to 15 percent of the general population. It\ncan manifest as either primary with origins that are not en-\ntirely clear, or secondary, linked to medical and gynecological\nissues such as iron deficiency anemia, chronic renal failure,\nperipheral neuropathy, pregnancy, and the use of certain an-\ntidepressant medications [2].\nPregnant women are particularly vulnerable to experienc-\ning RLS with rates that indicate the influence of ovarian hor-\nmones. However, our study excluded pregnant women to over-\ncome the possible effect of hormonal changes on precipitating\nRLS and ensure the correlation with endometriosis [17]. The\npresence of RLS symptoms in patients with gynecological dis-\norders, especially those with endometriosis, is important for\nmany reasons. Firstly, it is possible to identify common eti-\nological factors between the two conditions, leading to novel\ntherapeutic options. For example, iron deficiency anemia is a\nhttp://doi.org/10.33091/amj.2024.147487.1618 109\n\nMufeed Akram Taha Anb. Med. J. 20(1), 2024\nT able1. Sociodemographic characteristics among the study population.\nEndometriosis P-value ∗\nYes No\nNumber Percent Number Percent\nAge (Years)\n< 25 18 25.0% 19 22.9%\n0.02925–30 31 43.1% 23 27.7%\n31–35 17 23.6% 20 24.1%\n>35 6 8.3% 21 25.3%\nMartial state Married 63 87.5% 71 85.5% 0.72Single 9 12.5% 12 14.5%\nSmoking Yes 5 6.9% 3 3.6% 0.35No 67 93.1% 80 96.4%\nBMI(kg/m2)\nUnderweight < 18.5 2 2.8% 3 3.6%\n0.35Normal 18.5–24.9 11 15.3% 10 12.0%\nOverweight 25–29.9 40 55.6% 37 44.6%\nObese > 30 19 26.4% 33 39.8%\n* Pearson’s Chi-squared test, BMI=body mass index.\nT able2. Distribution of the studied groups according to the IRLSSG rating scale.\nIRLSSG score Endometriosis P-value ∗\nYes No\nNumber Percent Number Percent\nMild (1–10) 6 8.3% 28 33.7%\n0.001Moderate (11–20) 11 15.3% 33 39.8%\nSevere (21–30) 32 44.4% 11 13.3%\nVery severe (31–40) 23 31.9% 11 13.3%\n* Pearson’s Chi-squared test, IRLSSG = International restless leg syndrome studied group.\nFigure 1. Distribution of RLS patients according to rASRM\nscore of endometriosis. rASRM = revised American Society\nof Reproductive Medicine.\nrecognized cause of RLS [18]. In addition, evidence suggests\nthat women with endometriosis have a significantly reduced\nhemoglobin concentration and average cell volume compared\nto controls of the same age [12].\nIn this study, most patients were below 30 years old in cases\nT able 3. The correlation of the IRLSSG rating with the\nseverity of endometriosis.\nrASRM score\nIRLSSG rating scale\nPearson’s correlation 0.762 ∗\nSig. (2-tailed) 0.0001\nN 72\n* Strongly positive pearson correlation, IRLSSG = Interna-\ntional Restless Legs Syndrome Study Group, rASRM =\nrevised American Society of Reproductive Medicine.\nof RLS with endometriosis, which aligns with the findings of\nBulun et al.’s study [19]. In addition, about the BMI index\nand smoking habits, there was no significant association be-\ntween the two studied groups, which is similar to Pantelis et\nal.’s study [20] that failed to link BMI to endometriosis, as\nwell as the study of Coiplet et al. [21], which did not find a re-\nlationship between smoking and endometriosis. However, this\ncontradicts the study of Srivanitchapoom et al. [22], which\nidentified pregnancy, smoking, and obesity as risk factors for\nRLS. These discrepancies may be due to differences in sample\nsize or genetic influences on RLS, as well as the occurrence of\nendometriosis in the different populations examined.\nThe study found a correlation between the IRLSSG rat-\ning scale and the rASRAM endometriosis severity score, sup-\nporting the research that was conducted by Tempest and col-\n110 http://doi.org/10.33091/amj.2024.147487.1618\n\nRestless Leg Syndrome and Endometriosis Anb. Med. J. 20(1), 2024\nFigure 2. The correlation between restless leg syndrome rat-\ning scale and the severity of endometriosis. IRLSSG = In-\nternational restless leg syndrome Study Group, rASRM =\nRevised American Society of Reproductive Medicine.\nleagues [12]. The current study showed that there was a cor-\nrelation between RLS in women with surgically confirmed en-\ndometriosis, which showed a significant positive correlation\nbetween the severity of endometriosis and the RLS rating\nscale that is comparable to the study of Sumbodo et al. [13].\nThe correlation between these two conditions might be\ndue to shared factors or hormonal influences affecting both.\nOur study revealed that 46.3% of participants with RLS also\nhad endometriosis highlighting the importance of this corre-\nlation. However, our study had some limitations. Specifically\nwe did not exclude asymptomatic endometriosis cases, which\ncould have influenced our results and potentially underesti-\nmated the link between these conditions. Moreover we did\nnot consider parity, as a possible underlying cause of both\nconditions. Furthermore, the study design is a cross-sectional\ndesign over a specific time period imposed constraints on\nour research scope. Moreover, we did not explore how RLS\nand endometriosis symptoms coincide during menstruation,\nwhere endometriosis symptoms typically worsen. While, our\nfindings indicate a correlation between RLS severity and en-\ndometriosis they do not definitively establish whether one con-\ndition triggers the other or if there is a shared factor that\ncauses both conditions. To gain insights into the relationship\nbetween these two conditions and ascertain causality, addi-\ntional future prospective cohort studies are necessary.\nCONCLUSION\nThere was a correlation between RLS and endometriosis,\nbut the cause and nature of this relationship remain unclear.\nProspective studies are required to investigate the temporal\nsequence of events and uncover the underlying mechanisms\nlinking these two conditions.\nETHICAL DECLARA TIONS\nAcknoweldgements\nNone.\nEthics Approval and Consent to Participate\nEthics approval was obtained from the Clinical Research\nEthics Committee, College of Medicine, University of Kirkuk,\nKirkuk, Iraq (decision no. 32, date 10.04.2023). Informed\nconsent was obtained from all patients participating in the\nstudy.\nConsent for Publication\nNot applicable (no individual or personal data included).\nAvailability of Data and Material\nData is available upon reasonable request from the corre-\nsponding author.\nCompeting Interests\nThe author declares that there is no conflict of interest.\nF unding\nNo funding.\nAuthors’ Contributions\nTaha MA was responsible for the literature review, design\nof the study, collection of the data, statistical analysis, and\nwriting the manuscript. The author read and approved the\nfinal version of the manuscript.\nREFERENCES\n[1] F. Porta, A. Neirotti, and M. Spada. Restless legs syn-\ndrome in DNAJC12 deficiency. Neurological Sciences,\n44(6):2167–2172, 2023.\n[2] I. Kouri, M. R. Junna, and M. C. Lipford. Restless legs\nsyndrome and periodic limb movements of sleep: from\nneurophysiology to clinical practice. Journal of Clinical\nNeurophysiology, 40(3):215–223, 2023.\n[3] A. Brostr¨ om, Z. Alimoradi, J. Lind, M. Ulander,\nF. Lundin, and A. Pakpour. Worldwide estimation of\nrestless legs syndrome: A systematic review and meta-\nanalysis of prevalence in the general adult population.\nJournal of Sleep Research, 32(3):e13783, 2023.\n[4] A. Amir, R. M. Masterson, A. Halim, and A. Nava. Rest-\nless leg syndrome: pathophysiology, diagnostic criteria,\nand treatment. Pain Medicine, 23(5):1032–1035, 2022.\n[5] K. T. Zondervan, C. M. Becker, and S. A. Miss-\nmer. Endometriosis. New England Journal of Medicine ,\n382(13):1244–1256, 2020.\n[6] C.-C. Chiu et al. Maintenance Therapy for Preventing\nEndometrioma Recurrence after Endometriosis Resec-\ntion Surgery–A Systematic Review and Network Meta-\nanalysis. Journal of Minimally Invasive Gynecology ,\n29(5):602–612, 2022.\n[7] L. M. Van Niekerk, B. Dell, L. Johnstone, M. Matthew-\nson, and M. Quinn. Examining the associations between\nhttp://doi.org/10.33091/amj.2024.147487.1618 111\n\nMufeed Akram Taha Anb. Med. J. 20(1), 2024\nself and body compassion and health related quality of\nlife in people diagnosed with endometriosis. Journal of\nPsychosomatic Research, 167:111202, 2023.\n[8] C. Geng, Z. Yang, X. Kong, P. Xu, and H. Zhang. As-\nsociation between thyroid function and disease sever-\nity in restless legs syndrome. Frontiers in Neurology ,\n13:974229, 2022.\n[9] A. Zali et al. The prevalence of restless legs syndrome\n(RLS) in patients with multiple sclerosis (MS): A system-\natic review and meta-analysis—An update. Neurological\nSciences, 44(1):67–82, 2023.\n[10] P. Ning, X. Mu, X. Yang, T. Li, and Y. Xu. Prevalence of\nrestless legs syndrome in people with diabetes mellitus:\nA pooling analysis of observational studies. E Clinical\nMedicine, 46:101357, 2022.\n[11] M. Caltekin, M. Hamamci, T. Onat, D. Kirmizi,\nE. Ba¸ ser, and E. YALVAC ¸ . Evaluation of sleep quality,\nrestless legs syndrome, anxiety and depression in polycys-\ntic ovary syndrome. JOURNAL OF TURKISH SLEEP\nMEDICINE-TURK UYKU TIBBI DERGISI, 8(3), 2021.\n[12] N. Tempest, M. Boyers, A. Carter, S. Lane, and D. K.\nHapangama. Premenopausal women with a diagnosis of\nendometriosis have a significantly higher prevalence of\na diagnosis or symptoms suggestive of restless leg syn-\ndrome: a prospective cross-sectional questionnaire study.\nFrontiers in Endocrinology, 12:599306, 2021.\n[13] C. D. Sumbodo, K. Tyson, S. Mooney, J. Lamont,\nM. McMahon, and S. J. Holdsworth-Carson. The rela-\ntionship between sleep disturbances and endometriosis:\nA systematic review. European Journal of Obstetrics &\nGynecology and Reproductive Biology, 293:1–8, 2023.\n[14] R. P. Allen et al. Restless legs syndrome/Willis–Ekbom\ndisease diagnostic criteria: updated International Rest-\nless Legs Syndrome Study Group (IRLSSG) consensus\ncriteria–history, rationale, description, and significance.\nSleep medicine, 15(8):860–873, 2014.\n[15] M. Canis et al. Revised american society for reproductive\nmedicine classification of endometriosis: 1996. Fertility\nand Sterility, 67(5):817–821, 1997.\n[16] D. Mohajan and H. K. Mohajan. Body mass index\n(BMI) is a popular anthropometric tool to measure obe-\nsity among adults. Journal of Innovations in Medical\nResearch, 2(4):25–33, 2023.\n[17] M. Na, J. Wu, M. Li, S. N. Hinkle, C. Zhang, and X. Gao.\nNew onset of restless legs syndrome in pregnancy in a\nprospective multiracial cohort: Incidence and risk fac-\ntors. Neurology, 95(24):e3438–e3447, 2020.\n[18] Y.-S. Li, W.-C. Yeh, and C.-Y. Hsu. Association of low\nserum ferritin levels with augmentation in patients with\nrestless legs syndrome: A systematic review and meta-\nanalysis. Sleep Medicine, 112:173–180, 2023.\n[19] S. E. Bulun and B. D. Yilmaz. Sison Ch., Miyazaki K.,\nBernardi L., Liu Sh. et al. Endometriosis. Endocr. Rev,\n40(4):1048–1079, 2019.\n[20] A. Pantelis, N. Machairiotis, and D. P. Lapatsanis. The\nformidable yet unresolved interplay between endometrio-\nsis and obesity. The Scientific World Journal, 2021:1–10,\n2021.\n[21] E. Coiplet, B. Courbiere, A. Agostini, L. Boubli,\nF. Bretelle, and A. Netter. Endometriosis and environ-\nmental factors: A critical review. Journal of Gynecology\nObstetrics and Human Reproduction, 51(7):102418, 2022.\n[22] P. Srivanitchapoom, S. Pandey, and M. Hallett. Restless\nlegs syndrome and pregnancy: a review. Parkinsonism\n& related disorders, 20(7):716–722, 2014.\n112 http://doi.org/10.33091/amj.2024.147487.1618","source_license":"CC0","license_restricted":false}